CN107629095B - Terminal-selective deprotection of peracetyl sugars catalyzed by hafnium triflate - Google Patents

Abstract

The invention relates to a selective deprotection method of a peracetyl sugar end position, which takes hafnium trifluoromethanesulfonate as a catalytic reagent, respectively takes peracetylated monosaccharide, disaccharide and trisaccharide as substrates, and acetonitrile containing a proper amount of water as a solvent, and can selectively and efficiently remove the acetyl at the 1-O position of the substrate under the condition of proper heating. The hafnium trifluoromethanesulfonate used in the invention has high catalytic activity and small dosage (the optimal catalytic effect can be achieved only by 2 mol%), and is generally suitable for various fully acetylated monosaccharides (D-type, L-type, pyran type and furan type), disaccharides and trisaccharide substrates (the separation yield can reach 82-95%). The method for catalyzing the hafnium trifluoromethanesulfonate has the advantages of mild reaction conditions (only 60 ℃ is needed for heating), no need of inert gas protection for a reaction system, and simple post-treatment and purification methods.

Description

Terminal-selective deprotection of peracetyl sugars catalyzed by hafnium triflate

technical field

The invention belongs to the technical field of chemical preparation of organic compounds, and relates to a method and process for the selective deprotection of peracetyl sugar terminal position catalyzed by hafnium trifluoromethanesulfonate.

Background technique

The regioselective deacetylation of the terminal position of peracetyl-protected sugar raw materials is of great significance in the field of sugar chemical synthesis. In oligosaccharide synthesis, peracetylated hemiacetal sugar, that is, the product after selective deprotection of the 1-O position of peracetylated sugar, can be further converted into glycosyl trichloroacetimide, halosugar, Activated glycosyl fragments such as glycosyl phosphates are used for the construction of glycosidic bonds. In addition, peracetylated hemiacetal is also an important synthetic building block for the synthesis of various bioactive glycosyl conjugates.

At present, there are two main types of selective deprotection methods for the terminal position of peracetyl sugars reported in the literature. One is to use various nitrogen-containing nucleophilic (ammonia/amine) reagents to remove the terminal acetyl group by amidation reaction. The main problems with this type of process are that large excesses of ammonia/amines are usually required and many reagents are toxic. Another method is to use protic acid or Lewis acid reagent to remove the acetyl group at the terminal position of sugar group by alcoholysis or hydrolysis reaction. At present, there are only a few metal Lewis acid catalysts reported in the literature, such as tributyltin alkoxide, copper acetate, ferric chloride, mercuric oxide/mercuric chloride, neodymium trifluoromethanesulfonate, and zinc acetate. The removal yield of terminal acetyl group is generally only about 70-80%, and some are even lower. Among them, only neodymium trifluoromethanesulfonate and zinc acetate are used in catalytic amounts (5-10% equivalent), and the rest of the catalysts need to be used in equivalent or even excess amounts. Moreover, since methanol is used as a solvent in the reaction system of neodymium trifluoromethanesulfonate and zinc acetate, it is easy to generate by-products of acetyl polysaccharide or cause forsylation at the terminal position of sugar groups in practical applications. Therefore, finding an efficient, versatile and highly regioselective metal Lewis acid catalyst for the terminal-selective deprotection of peracetylated sugars has great practicality for the preparation of peracetylated hemiacetals as well as for the overall sugar chemical synthesis. Value.

SUMMARY OF THE INVENTION

The purpose of the present invention is to find an efficient, versatile and highly regioselective metal Lewis catalyst for the terminal-selective deacetylation of peracetyl sugar, establish an optimized reaction system, and obtain corresponding reaction conditions and processes.

Reaction scheme of the present invention is:

The terminal-selective deprotection method of peracetyl sugar involved in the present invention uses hafnium trifluoromethanesulfonate as a catalytic reagent, peracetylated monosaccharide, disaccharide and trisaccharide as substrates respectively, and acetonitrile containing an appropriate amount of water as solvent , the 1-O acetyl group of the substrate can be selectively and efficiently removed under appropriate heating conditions. The crude product was purified by conventional silica gel column chromatography to obtain 11 peracetylhemiacetal products (1–11) in high yield.

The chemical formulas of the 11 peracetylhemiacetal sugar products (1–11) are as follows:

In this method, in order to optimize the reaction rate, selectivity and yield, the amount of the used hafnium trifluoromethanesulfonate catalytic reagent should be strictly controlled to be 2 mol% (that is, 0.02 times the equivalent), and the ideal reaction solvent needs to use a Acetonitrile with a water content of 0.3% (volume ratio) was used as a solvent, and the ideal concentration of the substrate in the reaction solution was 0.15M (too concentrated or too dilute will affect the reaction rate and product yield). The reaction temperature must be strictly controlled at 60°C (otherwise it will reduce the reaction rate or cause side reactions to reduce the product yield). The reaction system does not need to be protected by an inert gas, and the system can be opened. The reaction time of peracetyl monosaccharide was 6 hours, and the reaction time of peracetyl disaccharide and trisaccharide was slightly longer, requiring 8 hours. In the post-treatment of the method, only the reaction system needs to be concentrated, and the conventional silica gel column chromatography can be performed directly.

Compared with the methods reported in the literature in the past, the hafnium trifluoromethanesulfonate used in the patent of the present invention has high catalytic activity and low consumption (only 2 mol% is needed to achieve the best catalytic effect), and is generally applicable to various peracetylated monohydrates. Sugar (D-, L-, pyran, furan), disaccharide and trisaccharide substrates (82–95% isolated yield). The method catalyzed by hafnium trifluoromethanesulfonate has mild reaction conditions (only needs to be heated at 60° C.), the reaction system does not need to be protected by an inert gas, and the post-processing and purification methods are simple.

Detailed ways

Embodiment 1:

Synthesis of 2,3,4-triacetyl-L-rhamnose (1): 1,2,3,4-tetraacetyl-L-rhamnose (2.0 g, 6.0 mmol) , Hafnium trifluoromethanesulfonate (93 mg, 0.12 mmol) was dissolved in acetonitrile (40 mL, [substrate]=0.15 M) with a water content of 0.3% (volume ratio), and the reaction was heated and stirred at 60° C. for 6 hours. The reaction solution was concentrated to obtain a crude product, and silica gel column chromatography (petroleum ether/ethyl acetate=2:1) gave 1.61 g of 2,3,4-triacetyl-L-rhamnose (1), with a yield of 92% .

Embodiment 2:

Synthesis of 2,3,4,6-tetraacetyl-D-glucopyranose (2): 1,2,3,4,6-pentaacetyl-D-glucopyranose (2.0 g, 5.1 mmol), Hafnium trifluoromethanesulfonate (79 mg, 0.10 mmol) was dissolved in acetonitrile (34 mL, [substrate]=0.15 M) with a water content of 0.3% (volume ratio), and the reaction was heated and stirred at 60°C for 6 hours. The reaction solution was concentrated to obtain a crude product, and silica gel column chromatography (petroleum ether/ethyl acetate=2:1) gave 1.61 g of 2,3,4,6-tetraacetyl-D-glucopyranose (2), with a yield of 90% .

Embodiment 3:

Synthesis of 2,3,4-triacetyl-D-xylopyranose (4): 1,2,3,4-tetraacetyl-D-xylopyranose (2.0 g, 6.3 mmol), tri- Hafnium fluoromethanesulfonate (98 mg, 0.13 mmol) was dissolved in acetonitrile (42 mL, [substrate]=0.15 M) with a water content of 0.3% (volume ratio), and the reaction was heated and stirred at 60° C. for 6 hours. The reaction solution was concentrated to obtain a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate=2:1) to obtain 1.62 g of 2,3,4-triacetyl-D-xylpyranose (4) with a yield of 93%.

Embodiment 4:

Synthesis of 2,3,5-triacetyl-D-ribofuranose (7): 1,2,3,5-tetraacetyl-D-ribofuranose (2.0 g, 6.3 mmol), trifluoromethanesulfonic acid Hafnium (98 mg, 0.13 mmol) was dissolved in acetonitrile (42 mL, [substrate]=0.15 M) with a water content of 0.3% (volume ratio), and the reaction was heated and stirred at 60° C. for 6 hours. The reaction solution was concentrated to obtain a crude product, which was subjected to silica gel column chromatography (petroleum ether/ethyl acetate=2:1) to obtain 1.63 g of 2,3,5-triacetyl-D-ribofuranose (7) with a yield of 94%.

Embodiment 5:

Synthesis of 4-(2,3,4,6-Tetraacetyl-α-D-glucopyranosyl)-2,3,6-triacetyl-D-glucopyranosyl (9) Disaccharide (4.0 g, 5.9 mmol), hafnium trifluoromethanesulfonate (91 mg, 0.12 mmol) were dissolved in acetonitrile (39 mL, [substrate] = 0.15 M) with a water content of 0.3% (volume ratio), heated and stirred at 60 °C The reaction was carried out for 8 hours. The reaction solution was concentrated to obtain crude product, and silica gel column chromatography (petroleum ether/ethyl acetate=2:1) obtained 4-(2,3,4,6-tetraacetyl-α-D-glucopyranosyl)-2, 3,6-Triacetyl-D-glucopyranose (9) 3.19 g, yield 85%.

Embodiment 6:

4-(4-(2,3,4,6-Tetraacetyl-α-D-glucopyranosyl)-2,3,6-triacetyl-α-D-glucopyranosyl)-2, Synthesis of 3,6-triacetyl-D-glucopyranose (11): Dissolve peracetyl-protected maltotriose (5.0 g, 5.2 mmol) and hafnium trifluoromethanesulfonate (81 mg, 0.1 mmol) in water content 0.3% (volume ratio) acetonitrile (35 mL, [substrate]=0.15M) was heated and stirred at 60°C for 8 hours. The reaction solution was concentrated to obtain crude product, and silica gel column chromatography (petroleum ether/ethyl acetate=2:1) obtained 4-(4-(2,3,4,6-tetraacetyl-α-D-glucopyranosyl) -2,3,6-Triacetyl-α-D-glucopyranosyl)-2,3,6-triacetyl-D-glucopyranosyl (11) 3.92 g, yield 82%.

Claims (1)

1. The selective deprotection method for the terminal position of the holoacetyl sugar catalyzed by hafnium trifluoromethanesulfonate is characterized in that: hafnium trifluoromethanesulfonate is used as a catalytic reagent, peracetylated monosaccharide, disaccharide and trisaccharide are used as substrates, water-containing acetonitrile is used as a solvent, the 1-O-position acetyl of the substrate is selectively and efficiently removed under the heating condition, and the crude product is subjected to conventional silica gel column chromatography purification to obtain a peracetylated hemiacetal sugar product with high yield;

wherein, the dosage of the hafnium triflate catalytic reagent is 2 mol%, the reaction solvent is acetonitrile with the water content volume ratio of 0.3%, the concentration of the substrate in the reaction solution is 0.15M, the reaction temperature is 60 ℃, the reaction time of the peracetylated monosaccharide is 6 hours, and the reaction time of the peracetylated disaccharide and the trisaccharide is 8 hours.